Elevated blood pressure is an important cardiovascular risk factor. The commonly assessed components of blood pressure are systolic pressure and diastolic pressure, corresponding to the peak and trough of the blood pressure waveform, respectively. Recently, "pulse pressure," or the difference between peak and trough pressure, has also been shown to be an important cardiovascular risk factor. In fact, in some patient populations, it may be the most important measure of blood pressure.
The basis for this association is presumed to be increased stiffness of the aorta and large conduit blood vessels as a result of age, arteriosclerosis, and other factors. However, this association remains presumptive, in large part due to a limited ability to directly, accurately, and non-invasively measure aortic stiffness. Such reliable measurements are needed for directly establishing a relationship between vessel stiffness and cardiac events, and for evaluating the effects of new treatments aimed at reducing conduit vessel stiffness.
One reliable measure of vessel stiffness is the velocity at which a pressure or flow wave travels in the vessel, known as the "pulse wave velocity." It is currently difficult to non-invasively measure pulse wave velocity in the most highly compliant segment of the aorta that traverses the thorax and provides a substantial proportion of the buffering capacity of the arterial system. One major difficulty is the limited ability to obtain reliable pressure or flow waveform data from two sites within this segment of the aorta using minimal intervention. Another difficulty lies in accurately defining the distance and transit time between the recording sites.
One approach has been to record pressure or flow waveforms in the carotid and femoral arteries, which are located at opposite ends of the section of aorta in question. This technique suffers from two major difficulties. First, it is impossible to determine the appropriate transit between the two sites because there is parallel simultaneous transmission of the advancing wave up the carotid artery and down the aorta. Furthermore, the radically diverse properties of the entire aorta, carotid artery, iliac arteries, and femoral artery will influence the transit time, making it difficult to determine the specific properties of the highly compliant segment of the thoracic aorta. A related approach uses Doppler ultrasound to determine flow waveforms at the site of the left subclavian artery and the abdominal aorta. This technique suffers from parallel transmission in the subclavian region and from considerable susceptibility to parallax error at the site of transabdominal insonation of the aorta in the periumbilical region.
Echocardiography and magnetic resonance imaging have been utilized to obtain waveforms in the proximal and distal aorta. Both techniques have dual imaging/flow capability, making it possible to determine the location of measurement of the flow waveform. Echocardiography has excellent flow resolution, but does not allow for quantification of the complex, curvilinear distance between the measuring sites, which are generally taken in the ascending aorta and in the descending aorta near the diaphragm. Magnetic resonance imaging allows for precise quantification of this transit distance, but suffers from poor temporal resolution of the flow waveform. Combined, they provide for accurate yet cumbersome and extremely expensive measurement of pulse wave velocity.
A further difficulty encountered in attempting to evaluate changes in the intrinsic stiffness of the arterial wall through the measurement of pulse wave velocity lies in the dependence of arterial stiffness on distending pressure. The elasticity of the arterial wall is nonlinear, with stiffness increasing as distending pressure increases within the physiological range of blood pressure. As blood pressure may vary considerably in a patient during the day or during the stress associated with a visit to the physician's office, it is desirable to establish the pressure-corrected or pressure-independent pulse wave velocity as a measure of intrinsic arterial stiffness. It is possible to administer medications that acutely raise or lower the blood pressure to the desired range and then to measure pulse wave velocity at this target blood pressure. However, these medications may also alter the intrinsic stiffness of the artery through direct or indirect effects on the muscle layer within the arterial wall. Such an approach is also time consuming and carries a small but quantifiable risk to the patient.
Finally, a number of recently developed devices claim to evaluate total arterial compliance utilizing a variety of algorithms. Without discussing the limitations of these devices in too much detail, it suffices to note that total arterial compliance, to which these devices relate, is not the same as proximal aortic stiffness, to which the present invention relates.
Accordingly, it is a primary object of the present invention to provide a method and device for accurately and safely determining the pulse wave velocity of blood in a blood vessel.
A more specific object is to provide a method and device for non-invasively measuring the pulse wave velocity of blood in the descending thoracic aorta.
Another object of the present invention is to provide a method and device for evaluating the pressure dependence of pulse wave velocity of blood in a blood vessel.
Yet another object of the present invention is to provide a pulse wave velocity measurement method and device that allows for easy and accurate determination of the distance between vessel measurement sites.
Still another object is to provide a method and device for determining a pressure-independent pulse wave velocity as a measure of intrinsic arterial stiffness.